Vitamin A deficiency dramatically influences the integrity of epithelial tissues by producing necrotic changes and induces proliferation and activation of the undifferentiated cell population. The effect of vitamin A deficiency on proliferating hepatocytes is similar to its effect on epithelial tissue in general; that is, cellular necrosis, uncontrolled proliferation and activation of the undifferentiated cell (oval cells, hepatic stem cells) population. In contrast to the vitamin A-supplemented rats, the level of epidermal growth factor receptor (EGFR) increased after partial hepatectomy in the deficient animals. The lack of ligand, retinoic acid (RA), for retinoic acid receptors (RARs) seems to lead to an increased expression of EGFR which, under normal conditions, is regulated by the RA/RAR system. Increase in the expression of transforming growth factor-alpha (TGF-alpha) is also observed in vitamin A-deficient animals and suggests that TGF-alpha/EGFR plays an important role in the activation of the stem cell compartment and in the proliferation of hepatocytes after partial hepatectomy of vitamin A deficient animals. The stem cell factor (SCF)/c-kit system, known to be important in the differentiation and proliferation of hemopoietic stem cells, appears also to affect the preservation and activation of the liver stem cell compartment in acetylaminofluorene/ partial hepatectomy (AAF/PH) model. The receptor, c- kit, is present in the early progeny of oval cells, whereas it is absent in both quiescent and proliferating hepatocytes. In contrast the ligand SCF is present both in the oval cells and in the perisinusoidal stellate cells. The distribution of two high affinity receptors, bek and flg, for acidic fibroblast growth factor (aFGF) was different in the oval cell compartment; flg was present only in the oval cells and was absent in the hepatocytes, whereas the transcripts for bek were found both in oval cells and in the perisinusoidal stellate cells as well as in the hepatocytes. These data suggest that the aFGF/flg system may represent a unique mechanism of signal transduction in oval cells which may lead to their differentiation into hepatocytes.